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Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin

A crucial bacterial strategy to avoid killing by antibiotics is to enter a growth arrested state, yet the molecular mechanisms behind this process remain elusive. The conditional overexpression of mazF, the endoribonuclease toxin of the MazEF toxin–antitoxin system in Staphylococcus aureus, is one a...

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Autores principales: Sierra, Roberto, Prados, Julien, Panasenko, Olesya O, Andrey, Diego O, Fleuchot, Betty, Redder, Peter, Kelley, William L, Viollier, Patrick H, Renzoni, Adriana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470975/
https://www.ncbi.nlm.nih.gov/pubmed/32735661
http://dx.doi.org/10.1093/nar/gkaa617
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author Sierra, Roberto
Prados, Julien
Panasenko, Olesya O
Andrey, Diego O
Fleuchot, Betty
Redder, Peter
Kelley, William L
Viollier, Patrick H
Renzoni, Adriana
author_facet Sierra, Roberto
Prados, Julien
Panasenko, Olesya O
Andrey, Diego O
Fleuchot, Betty
Redder, Peter
Kelley, William L
Viollier, Patrick H
Renzoni, Adriana
author_sort Sierra, Roberto
collection PubMed
description A crucial bacterial strategy to avoid killing by antibiotics is to enter a growth arrested state, yet the molecular mechanisms behind this process remain elusive. The conditional overexpression of mazF, the endoribonuclease toxin of the MazEF toxin–antitoxin system in Staphylococcus aureus, is one approach to induce bacterial growth arrest, but its targets remain largely unknown. We used overexpression of mazF and high-throughput sequence analysis following the exact mapping of non-phosphorylated transcriptome ends (nEMOTE) technique to reveal in vivo toxin cleavage sites on a global scale. We obtained a catalogue of MazF cleavage sites and unearthed an extended MazF cleavage specificity that goes beyond the previously reported one. We correlated transcript cleavage and abundance in a global transcriptomic profiling during mazF overexpression. We observed that MazF affects RNA molecules involved in ribosome biogenesis, cell wall synthesis, cell division and RNA turnover and thus deliver a plausible explanation for how mazF overexpression induces stasis. We hypothesize that autoregulation of MazF occurs by directly modulating the MazEF operon, such as the rsbUVW genes that regulate the sigma factor SigB, including an observed cleavage site on the MazF mRNA that would ultimately play a role in entry and exit from bacterial stasis.
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spelling pubmed-74709752020-09-09 Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin Sierra, Roberto Prados, Julien Panasenko, Olesya O Andrey, Diego O Fleuchot, Betty Redder, Peter Kelley, William L Viollier, Patrick H Renzoni, Adriana Nucleic Acids Res Molecular Biology A crucial bacterial strategy to avoid killing by antibiotics is to enter a growth arrested state, yet the molecular mechanisms behind this process remain elusive. The conditional overexpression of mazF, the endoribonuclease toxin of the MazEF toxin–antitoxin system in Staphylococcus aureus, is one approach to induce bacterial growth arrest, but its targets remain largely unknown. We used overexpression of mazF and high-throughput sequence analysis following the exact mapping of non-phosphorylated transcriptome ends (nEMOTE) technique to reveal in vivo toxin cleavage sites on a global scale. We obtained a catalogue of MazF cleavage sites and unearthed an extended MazF cleavage specificity that goes beyond the previously reported one. We correlated transcript cleavage and abundance in a global transcriptomic profiling during mazF overexpression. We observed that MazF affects RNA molecules involved in ribosome biogenesis, cell wall synthesis, cell division and RNA turnover and thus deliver a plausible explanation for how mazF overexpression induces stasis. We hypothesize that autoregulation of MazF occurs by directly modulating the MazEF operon, such as the rsbUVW genes that regulate the sigma factor SigB, including an observed cleavage site on the MazF mRNA that would ultimately play a role in entry and exit from bacterial stasis. Oxford University Press 2020-09-04 2020-07-31 /pmc/articles/PMC7470975/ /pubmed/32735661 http://dx.doi.org/10.1093/nar/gkaa617 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Molecular Biology
Sierra, Roberto
Prados, Julien
Panasenko, Olesya O
Andrey, Diego O
Fleuchot, Betty
Redder, Peter
Kelley, William L
Viollier, Patrick H
Renzoni, Adriana
Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin
title Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin
title_full Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin
title_fullStr Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin
title_full_unstemmed Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin
title_short Insights into the global effect on Staphylococcus aureus growth arrest by induction of the endoribonuclease MazF toxin
title_sort insights into the global effect on staphylococcus aureus growth arrest by induction of the endoribonuclease mazf toxin
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470975/
https://www.ncbi.nlm.nih.gov/pubmed/32735661
http://dx.doi.org/10.1093/nar/gkaa617
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